Women of childbearing age and infants have become the fastest growing HIV- infected segment of the U.S. population. Approximately one-third of children born to HIV-infected mothers are themselves infected at birth. The reasons why two-thirds of children are protected from infection are unknown. The pig-tailed macaque (Macaca nemestrina) is an unusually SIV- susceptible macaque species that develops a fatal immunosuppressive disease characterized by CD4 depletion and opportunistic infections. We have developed a macaque model for maternal-fetal transmission of retroviruses by infecting pregnant pig-tailed macaques with pathogenic SIV/Mne. The incidence of maternal fetal transmission was 33%, similar to that observed in children born to HIV-1 infected mothers. Pregnant pig- tailed macaques were also inoculated intravenously and/or intra- amniotically with HIV-1. Three of five pregnant macaques became HIV-1 virus positive by culture, and four seroconverted. One aborted infant with severe chorioamnionitis had HIV-1 antigens in lymphoid organs and brain. One infant, HIV-1 culture positive at age 4 days, died at age 11 days and at necropsy was found to have disseminated HIV-1 infection. This macaque model will be useful for determining the factors affecting transmission of SIV and HIV from mother to infant, as well as the effectiveness of antiviral therapy in preventing infection in newborns. We have also inoculated macaques intrarectally with various dilutions of SIV. Some animals, exposed to doses of SIV below the threshold required for virus isolation or seroconversion, developed CD4 cell depletion up to 4 years following inoculation. These results may be applicable to the idiopathic CD4+ T-lymphocytopenia which has been reported in patients for whom there is no evidence of HIV infection. In addition, animals infected intrarectally with a dose of SIV below the level required for seroconversion had lymphocytes that were able to proliferate in response to SIV viral antigens. These macaques will be challenged with an infec- tious dose of SIV to determine if they are now protected from infection.